RNA interference (RNAi) is a sequence-specific gene silencing mechanism. This process can be induced artificially by introducing into the cell a RNAi agent targeting a particular sequence. Many structures are suitable for RNAi agents, including but not limited to short interfering RNAs (siRNAs). RNAi agents can have any of a variety of structures, including double-stranded RNA, which can be modified.
RNAi agents are desirable for therapeutic use. However, this use is limited by a short duration of activity, sometimes mediated by the degradation of these molecules in blood serum. Naked RNAi agents often have a half-life of minutes. Layzer et al. 2004 RNA 10: 766-771; Choung et al. 2006 Biochem. Biophys. Res. Comm. 342: 919-927; Sato et al. 2007 J. Control. Rel. 122: 209-216.
There thus exists the need for novel modifications for RNAi agents which do not interfere with RNA interference activity, but which increase the activity, biological half-life in blood serum, and/or duration of activity.
RNAi agents with these modifications would be useful in methods of target-specific silencing via the RNA interference mechanism.